What is Stress

In technical terms stress is a disruption of homeostasis, triggered by either real or perceived physical or psychological stimuli. Simply put an action or thought that disrupts normal balance.

Stress is a term that is used often to describe many feelings or emotions. Anxiety, depression, distress, fear, and exhaustion are just some of these and are all feelings that can be described as stress.

The term “stress” had none of its contemporary connotations before the 1920s. It is a form of the Middle English destresse, derived via Old French from the Latin stringere, “to draw tight.” The word had long been in use in physics to refer to the internal distribution of a force exerted on a material body, resulting in strain.

In the 1920s and ’30s, biological and psychological circles occasionally used the term to refer to a mental strain or to a harmful environmental agent that could cause illness.

Physiological stress represents a wide range of physical responses that occur as a direct effect of a stressor causing an upset in the homeostasis of the body. Upon immediate disruption of either psychological or physical equilibrium the body responds by stimulating the nervous, endocrine, and immune systems. The reaction of these systems causes a number of physical changes that have both short- and long-term effects on the body.

Neuroanatomy of Stress

The brain plays a critical role in the body’s perception of and response to stress. However, pinpointing exactly which regions of the brain are responsible for particular aspects of a stress response is difficult and often unclear.

Understanding that the brain works in more of a network-like fashion carrying information about a stressful situation across regions of the brain (from cortical sensory areas to more basal structures and vice versa) can help explain how stress and its negative consequences are heavily rooted in neural communication dysfunction. In spite of this, several important brain structures implicated in playing key roles in stress response pathways are described below:

Hypothalamus

The hypothalamus is a small portion of the brain located below the thalamus and above the brainstem. One of its most important functions is to help link together the body’s nervous and endocrine systems. This structure has many bidirectional neural inputs and outputs from and to various other brain regions.

These connections help to regulate the hypothalamus’ ability to secrete hormones into the body’s blood stream, having far-reaching and long-lasting effects on physiological processes such as metabolism. During a stress response, the hypothalamus secretes various hormones, namely corticotropin-releasing hormone, which stimulates the body’s pituitary gland and initiates a heavily regulated stress response pathway.

Amygdala

The amygdala is a small, “almond”-shaped structure, two of which are located bilaterally and deep within the medial temporal lobes of the brain. The amygdalae are part of the brain’s limbic system, with projections to and from the hypothalamus, hippocampus, and locus coeruleus among other areas.

Thought to play a role in the processing of emotions, the amygdalae have been implicated in modulating stress response mechanisms, particularly when feelings of anxiety or fear are involved.

Hippocampus

The hippocampus is a structure located bilaterally, deep within the medial temporal lobes of the brain, just below each amygdala, and is a part of the brain’s limbic system. The hippocampus is thought to play an important role in memory formation. There are numerous connections to the hippocampus from the cerebral cortex, hypothalamus, and amygdala, among other regions.

During stress, the hippocampus is particularly important, in that cognitive processes such as prior memories can have a great influence on enhancing, suppressing, or even independently generating a stress response. The hippocampus is also an area in the brain that is susceptible to damage brought upon by chronic stress.

Prefrontal cortex

The prefrontal cortex, located in the frontal lobe, is the anterior-most region of the cerebral cortex. An important function of the prefrontal cortex is to regulate cognitive processes including planning, attention and problem solving through extensive connections with other brain regions. The prefrontal cortex can become impaired during the stress response.

Locus coeruleus

The locus coeruleus is an area located in the pons of the brainstem that is the principal site of the synthesis of the neurotransmitter norepinephrine, which plays an important role in the sympathetic nervous system’s fight-or-flight response to stress. This area receives input from the hypothalamus, amygdala, and raphe nucleus among other regions and projects widely across the brain as well as to the spinal cord.

Raphe nucleus

The raphe nucleus is an area located in the pons of the brainstem that is the principal site of the synthesis of the neurotransmitter serotonin, which plays an important role in mood regulation, particularly when stress is associated with depression and anxiety. Projections extend from this region to widespread areas across the brain, namely the hypothalamus, and are thought to modulate an organism’s circadian rhythm and sensation of pain among other processes.

Biological Mechanisms

The peripheral nervous system (PNS) consists of two subsystems: the somatic nervous system and the autonomic nervous system. When a physical stressor acts upon the body the sensory-somatic nervous system is triggered through stimulation of the body’s sensory nerves. The signal acts as a nerve impulse and travels through the body in a process of electrical cell-to-cell communication until it reaches the automatic nervous system.

Activation of the automatic nervous system immediately triggers a series of involuntary chemical responses throughout the body. Preganglionic neurons release the neurotransmitter acetylcholine (ACh). This stimulates postganglionic neurons which release noradrenaline. The noradrenaline flows directly into the bloodstream ensuring that all cells in the body’s nervous and endocrine systems have been activated even in areas which the ganclionic neurons are unable to reach.

Endocrine system

When a stressor acts upon the body, the endocrine system is triggered by the release of the neurotransmitter noradrenaline by the autonomic nervous system. Noradrenaline stimulates the hypothalamic-pituitary-adrenal axis (HPA) which processes the information about the stressor in the hypothalamus.

This quickly signals the pituitary gland and finally triggers the adrenal cortex. The adrenal cortex responds by signaling the release of the corticosteroids cortisol and corticotropin releasing hormone (CRH) directly into the bloodstream.

Central nervous system (CNS)

The central nervous system (CNS) is made up of the brain and the spinal cord. The brain is equipped to process stress in three main areas: the amygdala, the hippocampus, and the prefrontal cortex. Each of these areas is densely packed with stress corticosteroid receptors which process the intensity of physical and psychological stressors acting upon the body through a process of hormone reception.

There are two types of corticosteroid receptors: mineralocorticoid receptors and glucocorticoid receptors. The mineralocorticoid receptors (MR) have an extremely high affinity for cortisol. This means that they are at least partially stimulated at all times and therefore are entirely activated almost immediately when a true stressor is disrupting the homeostasis of the body. The second type of receptor, glucocorticoid receptors (GR), have a low affinity for cortisol and only begin to become activated as the sensation of stress reaches its peak intensity on the brain.

Stress dramatically reduces the ability of the blood brain barrier (BBB) to block the transfer of chemicals including hormones from entering the brain from the bloodstream. Therefore when corticosteroids are released into the bloodstream – they are immediately able to penetrate the brain and bind to first the MR and then the GR.

As the GR begin to become activated, neurons in the amygdala, hippocampus, and prefrontal cortex become over stimulated. This stimulation of the neurons triggers a fight-or-flight response which allows the brain to quickly process information and therefore deal with life-threatening situations. If the stress response continues and becomes chronic, the hyperactivity of the neurons begins to physically change the brain and have severe damaging effects on one’s mental health.

As the neurons begin to become stimulated, calcium is released through channels in their cell membranes. Although initially this allows the cells chemical signals to continue to fire, allowing nerve cells to remain stimulated, if this continues the cells will become overloaded with calcium leading to over-firing of neuron signals. The over-firing of the neurons is seen to the brain as a dangerous malfunction; therefore, triggering the cells to shut down to avoid death due to over stimulation.

Decline in both neuroplasticity and long-term potentiation (LTP) occurs in humans after experiencing levels of high continual stress. To maintain homeostasis the brain is continuously forming new neural connections, reorganizing its neural pathways, and working to fix damages caused by injury and disease. This keeps the brain vital and able to perform cognitive complex thinking.

When the brain receives a distress signal it immediately begins to go into overdrive. Neural pathways begin to fire and rewire at hyper-speed to help the brain understand how to handle the task at hand.

Often, the brain becomes so intently focused on this one task that it is unable to comprehend, learn, or cognitively understand any other sensory information that is being thrown at it during this time. This over stimulation in specific areas and extreme lack of use in others causes several physiological changes in the brain to take place which overall reduce or even destroy the neuroplasticity of the brain.

Dendritic spines found of the dendrite of neurons begin to disappear and many dendrites become shorter and even less complex in structure. Glia cells begin to atrophy and neurogenesis often ceases completely. Without neuroplasticity, the brain loses the ability to form new connections and process new sensory information. Connections between neurons become so weak that it becomes nearly impossible for the brain to effectively encode long-term memories; therefore, the LTP of the hippocampus declines dramatically.

Stress is something that occurs all the time and affects everyone one way or another at least some of the time. Stress can be a good thing. It can be a source of motivation to help get something done or help one to react quickly to a potentially dangerous situation. The body reacts to stress by releasing more of the hormones cortisol and epinephrine.

Hypothalamic-pituitary-adrenal (HPA) axis

The HPA axis is a multi-step biochemical pathway where information is transmitted from one area of the body to the next via chemical messengers. Each step in this pathway, as in many biochemical pathways, not only passes information along to stimulate the next region but also receives feedback from messengers produced later in the pathway to either enhance or suppress earlier steps in the pathway – this is one way a biochemical pathway can regulate itself, via a feedback mechanism.

When the hypothalamus receives signals from one of its many inputs (e.g., cerebral cortex, limbic system, visceral organs) about conditions that deviate from an ideal homeostatic state (e.g., alarming sensory stimulus, emotionally charged event, energy deficiency), this can be interpreted as the initiation step of the stress-response cascade.

The hypothalamus is stimulated by its inputs and then proceeds to secrete corticotropin-releasing hormones. This hormone is transported to its target, the pituitary gland, via the hypophyseal portal system (short blood vessels system), to which it binds and causes the pituitary gland to, in turn, secrete its own messenger, adrenocorticotropic hormone, systemically into the body’s blood stream.

When adrenocorticotropic hormone reaches and binds to its target, the adrenal gland, the adrenal gland in turn releases the final key messenger in the cascade, cortisol. Cortisol, once released, has widespread effects in the body. During an alarming situation in which a threat is detected and signaled to the hypothalamus from primary sensory and limbic structures, cortisol is one way the brain instructs the body to attempt to regain homeostasis – by redistributing energy (glucose) to areas of the body that need it most, that is, toward critical organs (the heart, the brain) and away from digestive and reproductive organs, during a potentially harmful situation in an attempt to overcome the challenge at hand.

After enough cortisol has been secreted to best restore homeostasis and the body’s stressor is no longer present or the threat is no longer perceived, the heightened levels of cortisol in the body’s blood stream eventually circulate to the pituitary gland and hypothalamus to which cortisol can bind and inhibit, essentially turning off the HPA-axis’ stress-response cascade via feedback inhibition. This prevents additional cortisol from being released. This is biologically identified as a normal, healthy stress mechanism in response to a situation or stressor – a biological coping mechanism for a threat to homeostasis.

It is when the body’s HPA-axis cannot overcome a challenge and/or is chronically exposed to a threat that this system becomes overtaxed and can be harmful to the body and brain. A second major effect of cortisol is to suppress the body’s immune system during a stressful situation, again, for the purpose of redistributing metabolic resources primarily to fight-or-flight organs. While not a major risk to the body if only for a short period of time, if under chronic stress, the body becomes exceptionally vulnerable to immune system attacks. This is a biologically negative consequence of an exposure to a severe stressor and can be interpreted as stress in and of itself – a detrimental inability of biological mechanisms to effectively adapt to the changes in homeostasis.

Immune response

Cortisol can weaken the activity of the immune system. Cortisol prevents the proliferation of T-cells by rendering the interleukin-2 producer T-cells unresponsive to interleukin-1 (IL-1), and unable to produce the T-cell growth factor. Cortisol also has a negative-feedback effect on interleukin-1.

IL-1 must be especially useful in combating some diseases; however, endotoxic bacteria have gained an advantage by forcing the hypothalamus to increase cortisol levels (forcing the secretion of CRH hormone, thus antagonizing IL-1). The suppressor cells are not affected by glucosteroid response-modifying factor (GRMF), so the effective setpoint for the immune cells may be even higher than the setpoint for physiological processes (reflecting leukocyte redistribution to lymph nodes, bone marrow, and skin). Rapid administration of corticosterone (the endogenous Type I and Type II receptor agonist) orRU28362 (a specific Type II receptor agonist) to adrenalectomized animals induced changes in leukocyte distribution. Natural killer cells are not affected by cortisol.

Effect of stress on the immune system

Stress is the body’s reaction to any stimuli that disturbs its equilibrium. When the equilibrium of various hormones is altered the effect of these changes can be detrimental to the immune system. Much research has shown a negative effect stress has on the immune system, mostly through studies where participants were subjected to a variety of viruses. In one study individuals caring for a spouse with dementia, representing the stress group, saw a significant decrease in immune response when given an influenza-virus vaccine compared to a non-stressed control group.

A similar study was conducted using a respiratory virus. Participants were infected with the virus and given a stress index. Results showed that an increase in score on the stress index correlated with greater severity of cold symptoms. Studies with HIV have also shown stress to speed up viral progression. Men with HIV were 2–3 times more likely to develop AIDS when under above average stress.

Stress affects the immune system in many ways. The immune system protects the body from viruses, bacteria, and anything that is different or that the body does not recognize. The immune system sees these as intruders and it sends messages to attack. The white blood cells, leukocytes, are very important to the immune system.

White blood cells have several types including B cells, T cells, and natural killer cells. B cells secrete antibodies. T cells attack intruders and natural killer cells attack cells that have been infected by viruses. These leukocytes produce cytokines which fight infections.But they also are the immune systems communicator in telling the brain that the body is ill.

When an individual is stressed or going through a stressful experience the immune system starts to produce natural killer cells and cytokines. When levels of cytokines are higher they combat infections and therefore the brain gets communicated the body is ill and it produces symptoms as if the individual was ill. These symptoms include fever, sleepiness, lack of energy, no appetite, and basically flu like symptoms.

These symptoms mean the body is fighting the illness or virus. This is useful for when the body goes through the stress from an injury. But the body has now evolved to do this process during stressful events such as taking exams, or even going through a life changing event such as a death of a family member or a divorce. That is why many times when individuals are stressed because of life changing events or situations such as those, they get these symptoms and believe they are sick when in reality it can be because the body is under stress.

Effects of chronic stress

Chronic stress takes a more significant toll on the body than acute stress does. It can raise blood pressure, increase the risk of heart attack and stroke, increase vulnerability to anxiety and depression, contribute to infertility, and hasten the aging process. For example, results of one study demonstrated that individuals who reported relationship conflict lasting one month or longer have a greater risk of developing illness and show slower wound healing.

Similarly, the effects that acute stressors have on the immune system may be increased when there is perceived stress and/or anxiety due to other events. For example, students who are taking exams show weaker immune responses if they also report stress due to daily hassles. While responses to acute stressors typically do not impose a health burden on young, healthy individuals, chronic stress in older or unhealthy individuals may have long-term effects that are detrimental to health.

Mechanisms of chronic stress

Studies revealing the relationship between the immune system and the central nervous system indicate that stress can alter the function of the white blood cells involved in immune function known as lymphocytes and macrophages. People undergoing stressful life events, such as marital turmoil or bereavement, have a weaker lymphoproliferative response.

People in distressed marriages have also been shown to have greater decreases in cellular immunity functioning over time when compared to those in happier marriages. After antigens initiate an immune response, these white blood cells send signals, composed of cytokines and other hormonal proteins, to the brain and neuroendocrine system.

Cortisol, a hormone released during stressful situations, affects the immune system greatly by preventing the production of cytokines. During chronic stress, cortisol is over produced, causing fewer receptors to be produced on immune cells so that inflammation cannot be ended. A study involving cancer patient’s parents confirmed this finding. Blood samples were taken from the participants. Researchers treated the samples of the parents of cancer patients with a cortisol-like substance and stimulated cytokine production. Cancer patient parents’ blood was significantly less effective at stopping cytokine from being produced.

Chronic stress and memory

Chronic stress is seen to affect the parts of the brain where memories are processed through and stored. When people feel stressed, stress hormones get over-secreted, which affects the brain. This secretion is made up of glucocorticoids, including cortisol, which are steroid hormones that the adrenal gland releases, although this can increase storage of flashbulb memories it decreases long-term potentation (LTP).

Prolonged Stress can also be harmful to our body. That is because stress releases cortisol, and cortisol causes metabolic activity throughout the body. Metabolic activity is raised in the hippocampus. Overstimulation and toxins then are more likely to kill or damage neurons in the hippocampus.

The hippocampus is important in the brain for storing certain kinds of memories and damage to the hippocampus can cause trouble in storing new memories but old memories, memories stored before the damage, are not lost. Also high cortisol levels can be tied to the deterioration of the hippocampus and decline of memory that many older adults start to experience with age.

Stress Symptoms

Signs of stress may be cognitive, emotional, physical, or behavioral.

Cognitive symptoms

Memory problems

Inability to concentrate

Poor judgment

Pessimistic approach or thoughts

Anxious or racing thoughts

Constant worrying

Emotional symptoms

Moodiness

Irritability or short temper

Agitation, inability to relax

Feeling overwhelmed

Sense of loneliness and isolation

Depression or general unhappiness

Physical symptoms

Aches and pains

Diarrhea or constipation

Increased frequency of urination

Indigestion

Changes in blood glucose

Nausea, dizziness

Chest pain, rapid heartbeat

Loss of sex drive

Frequent colds

Irregular periods

Behavioral symptoms

Eating more or less

Sleeping too much or too little

Isolating oneself from others

Procrastinating or neglecting responsibilities

Using alcohol, cigarettes, or drugs to relax

Nervous habits (e.g. nail biting, pacing)

Types of Stressors

Both positive and negative stressors can lead to stress. These stressors can be physical or psychological. They themselves may not be the exact cause of stress as stress is more of a personal interpretation as far as adaptation resulting from personal experiences and the difference between what one might accept and what is expected.

One may have preconceived notions on how things are supposed to be and a variance can cause one stress. Many people often internalize events that occur even if they are not personally affected.

There are many factors that contribute to stress. Contributors to stress or stressors range from environmental factors like noise and light to world events such as war and natural disasters. Relationship troubles, work and school and lifestyle choices can all lead to stress.

Major Changes

Major life events or changes to ones life are the leading causes of stress as they are the most demanding on personal resources. Such changes include marriage or divorce, pregnancy or the death of a loved one, moving to a new location, changing jobs, etc. Stress can result from feelings or thoughts that one has.

What one considers stressful, another may not, and this is why stress is highly individual and personal in nature. Everyone has differing opinions, different ideas about the way things are or are supposed to be and various methods of coping.

Stress affects behavior, the mind and body in many different ways. There are symptoms of stress which like stress itself may vary from person to person in how they are observed or recognized. No matter whom you are too much stress can cause harm both emotionally and physically.